Anionic polymers as toxin binders

Abstract

The present invention relates to a method of inhibiting a toxin in an animal, such as a human, by administering to the animal a therapeutically effective amount of a polymer having a plurality of pendant acid functional groups which are directly attached to the polymer backbone or attached to the polymer backbone by a spacer group. The spacer group can have a length in the range from 0 to about 20 atoms. The toxin is, typically, an exotoxin secreted by a pathogenic microorganism, such as a bacterium.

What is claimed is:  
     
       1. A method for inhibiting a pathogenic toxin in a patient, comprising the step of administering to the patient a therapeutically effective amount of a polymer comprising pendant acid functional groups or a salt thereof with a pharmaceutically acceptable cation, said polymer comprising less than 2% acid anhydride groups. 
     
     
       2. The method of  claim 1  wherein the polymer further comprises a hyfrophobic group. 
     
     
       3. The method of  claim 1  wherein the acid functional group is a carboxylic acid, sulfonic acid, phosphonic acid, boronic acid, hydrosulfate or dihydrophosphate group. 
     
     
       4. The method of  claim 3  wherein the polymer comprises a monomer of Formula I,                    
       wherein X is a spacer group or a direct bond; R 1  and R 2  are each, independently, hydrogen or an alkyl group; or R 1  is a hydrogen atom or an alkyl group and R 2  is an acid functional group; and Y is an acid functional group. 
     
     
       5. The method of  claim 4  wherein X is normal, branched or cyclic, substituted or unsubstituted, saturated or unsaturated hydrocarbylene group or a normal branched or cyclic, substituted or unsubstituted, saturated or unsaturated hydrocarbylene group in which at least one carbon atom is substituted by a hereroatom. 
     
     
       6. The methos of  claim 5  wherein X is a C 2 -C 20 -alkylene group, a C 2 -C 20 -alkenylene group, a C 2 -C 20 -alkylene group interrupted at one or more points by a heteroatom, or a C 2 -C 20 -alkenylene group interrupted at one or more points by a heteroatom. 
     
     
       7. The method of  claim 6  wherein the heteroatom is a nitrogen, oxygen or sulfur atom. 
     
     
       8. The method of  claim 4  wherein the polymer is characterized by a repeat unit of Formula II,                    
       wherein R 1  and R 2  are each, independently, a hydrogen atom or an alkyl group; or R 1  is a hydrogen atom or an alkyl group and R 2  is an acid functional group; Z is O or NH, X is a spacer group and Y is an acid functional group. 
     
     
       9. The method of  claim 8  wherein X is a normal, branched or cyclic, substituted or unsubstituted, saturated or unsaturated hyfrocarbylene group or normal branched or cuclic, substituted or unsubstituted, saturated or unsaturated hydrocarbylene group in which at least one carbon atom is substituted by a heteroatom. 
     
     
       10. The method of  claim 9  wherein X is C 2 -C 20 - alkylene group, a C 2 -C 20 - alkenylene group, a C 2 -C 20 -alkylene group interrupted at one or more points by a heteroatom, or a C 2 -C 20 -alkenylene group interrupted at one or more points by a heteroatom. 
     
     
       11. The method of  claim 4  wherein the polymer is a copolymer. 
     
     
       12. The method of  claim 11  wherein the copolymer is a terpolymer. 
     
     
       13. The method of  claim 4  wherein the polymer is a copolymer which is further characterized by a monomer having a pendent hydrophobic group. 
     
     
       14. The method of  claim 13  wherein the hydrophobic group is a straight chain or branched, substituted or unsubstituted, cyclic or acyclic C 3 -C 24 -alkyl group, an aryl group or an arylalkyl group. 
     
     
       15. The method of  claim 12  wherein the polymer further comprises a neutral hydrophilic monomer. 
     
     
       16. The method of  claim 15  wherein the neutral hydrophilic monomer is selected from the group consisting of acrylamide, methacrylamide, N-(2-hydroxyethyl) acrylamide and 2-hydroxyethylmethacrylate. 
     
     
       17. The method of  claim 4  wherein the pathogenic toxin is a toxin associated with a microorganism selected from the group consisting of Streptococcus spp.; Salmonella spp.; Campylobacter spp.; Escherichia spp.; Vibrio spp.; Staphylococcus spp.; Shigella spp.; Pseudomonas spp.; Bordatella spp.; Listeria spp.; Yersinia spp.; Bacillus spp.; Helicobacter spp.; Corynebacteria spp.; Actinobacillus spp.; Aeromonas spp.; Bacteroides spp. and Pasteurella spp. 
     
     
       18. the method of  claim 17  wherein the microorganism is selected from the group consisting of  Streptococcus pneumoniae, Streptococcus pyogenes, Salmonella enteritidis, Campylobacter jejuni, Escherichia coli, Clostridium botulinum, Staphylococcus aureus, Shigella dysenteriae, Pseudomonas aeruginosa, Bordatella pertussis, Listeria monocytogenes, Yersinia enterocolitica, Legionella pneumophilia  and  Bacillus anthracis.    
     
     
       19. The method of  claim 17  wherein the microorganism is  Clostridium difficile.    
     
     
       20. The method of  claim 18  wherein the microorganism is a hemorrhagic  E. coli  strain. 
     
     
       21. The method of  claim 4  wherein the pathogenic toxin is a toxin associated with an organism selected from the group consisting of  Vibrio cholerae; Entameoba histolytica  and Acanthameoba. 
     
     
       22. A method for inhibiting a pathogenic toxin in a patent, said pathogenic toxin being produced by a bacterium, said method comprising the step of adminstering to the patient a therapuetically effective amount of a polymer comprising pendent acid functional groups or salt thereof with a pharmaceutically acceptable cation, said polymer comprising than less 2% acid anhydride groups. 
     
     
       23. The method of inhibiting a pathogenic toxin in a patient, said pathogenic toxin being produced by a fungus, said method comprising the step of administering to the patient a therapeutically effective amount of a polymer comprising pendent acid functional groups or a salt thereof with a phamaceutically acceptable cation, said polymer comprising than less 2% acid anhydride groups. 
     
     
       24. A method for inhibiting a pathogenic toxin in a patient, said pathogenic toxin being produced by a protozoan, said method comprising the step of administering to the patient a therapeutically effective amount of a polymer comprising pendant acid functional groups or salt thereof with a pharmaceutically a said polymer comprising than less 2% acid anhydride groups.